Liu Y,
Wang Y,
Dai W,
Huang W.
Li Y.
*
Liu H.
* Fudan University, Shanghai and Shanghai Institute of Materia Medica, P. R. of China
Palladium-Catalysed C(sp
3)–H Glycosylation for Synthesis of
C-Alkyl Glycoamino Acids.
Angew. Chem. Int. Ed. 2020;
59: 3491-3494
Key words
palladium catalysis - glycosylation - amino acids
Significance
The authors report a highly efficient, regio- and diastereoselective palladium-catalyzed glycosylation of inert β-C(sp3)–H bonds of N-phthaloyl α-amino acids under mild conditions. The method utilizes a combination of silver carbonate and trifluoroacetic acid in a polar solvent (THF), which enabled the activation cycle of this C–H bond. The reaction has a high tolerance towards functional groups and a broad scope, providing over 30 β-substituted C-alkyl glycoamino acids with up to 88% yield.
Comment
This method allows for the first time to activate C(sp3)–H bonds for glycosylation reactions, thus advancing the state-of-the-art techniques in carbohydrate chemistry. Liu and co-workers propose a mechanistic cycle for the C–H activation, based on experimental studies. Therein, the formation of a palladacycle via cyclometallation plays a key role in the activation and the resulting diastereoselectivity.
